Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the immune system maternal-fetal interface during palatal development

Abstract The maternal immune system during pregnancy is crucial for generating a balance between maternal immunity and the fetus. Our understanding of the potential impact of teratogens on the maternal-fetal interface (MFI) immune system and if such influences could precipitate the development of cleft palate (CP) remains limited. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widely prevalent environmental pollutant, was used as a teratogen to induce a CP animal model. Fifteen C57BL/6J mice were selected and randomly assigned to three groups: a control group, TCDD group, and TCDD plus Freund's complete adjuvant (FCA) group. Peripheral blood, placentas, and palatal tissues were collected for H&E, flow cytometry, and ELISA.In the TCDD group, the placental diameter, the number of placental labyrinth vessels, and the area of sponge layer cells were all significantly reduced. At embryonic day (E) 17.0, there was a significant decrease in T-helper 1 (Th1) and Th2 cells in the peripheral blood of pregnant mice. Additionally, the levels of Interferon-γ(IFN-γ) and Interleukin-4(IL-4), particularly IL-4, were significantly decreased. However, after treatment with FCA, the distance between the palatal shelves was reduced, and the placental weight, the number of labyrinth vessels and the area of the cavernous cells in the placenta also increased. The number of Th1 and Th2 cells significantly increased, returning to the levels observed in the control group, with a more pronounced increase in the number of Th2 cells.TCDD may induce CP by disrupting the homeostasis of the MFI. The precise mechanisms by which TCDD impact immune system at the MFI require further investigation.